Abstract
Classical swine fever (CSF) is a devastating disease that poses one of the greatest risks to the swine industry worldwide. Existing live attenuated CSF virus (CSFV) vaccines, such as the C-strain, provide a rapid onset of complete protection, but their application is limited due to an inability to discriminate infected amongst vaccinated animais. Many studies have aimed to develop marker sub-unit vaccines, but they frequently fail to show an appropriate level of efficacy for use under emergency outbreak conditions. An understanding of the immunological basis of rapid protection afforded by C-strain vaccine would aid the development of the next generation of marker CSFV vaccines. The first part of the study explored the interaction of porcine natural killer (NK) cells and yd-T cells with CSFV. Results suggest that is unlikely that these cells directly contribute to the cellular effector mechanisms induced by live attenuated CSFV, but rather they are modulated by the type I interferon (IFN) response triggered by CSFV infected plasmacytoid dendritic cells. Secondly, T cell responses following vaccination and subsequent challenge infections with virulent CSFV were characterised. The CD3+CD4-CD8 high T cell population was the first and major source of CSFV-specific IFN-γ and these cells were further characterised as CD107a+CD44 highCD62L- , expressing variable levels of CD25 and CD27 and subpopulations co-expressed tumor necrosis factor alpha (TNF-α) and interleukin 2 (IL-2). Finally, the specificity of virus-specific CD8 T cells was investigated by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. The results revealed immunodominance in the CD8 T cell response against CSFV, with antigen-specificity dependent on major histocompatibility complex class I (MHC-I) haplotype. It is hoped that the data generated by this study will inform on-going efforts to develop a safe and effective marker vaccine to improve the control of CSF.